1. Field of the Invention
The present invention relates to substituted aminoquinazolinone (thione) derivatives or salts thereof, intermediates thereof for preparing the same, pest controllers and a method for using the same.
2. Related Art
Japanese Patent Unexamined Publication, JP-A-8-325239 discloses that aminoquinazolinone derivatives are useful as pest controllers.
As a consequence of investigation earnestly conducted for finding a novel pest controller, the present inventors found that compounds of the present invention, having the substituents in the phenyl group which is belonging to the quinazolinone ring, possess the same or better insecticidal effects at low dosage as compared with compounds of Examples disclosed in the above-mentioned JP-A-8-325239. Particularly the compounds of the present invention possess sufficient insecticidal effects against whiteflies under consideration in the agricultural and horticultural fields, consequently the present inventors have accomplished the present invention.
The substituted aminoquinazolinone (thione) derivatives or salts thereof represented by the general formula (I) and the compounds represented by the general formula (II) which are intermediates for preparing the derivatives of the general formula (I) are novel compounds which have not been known in any prior art literature. Furthermore, pest controllers containing, as the active ingredient, the substituted aminoquinazolinone (thione) derivative represented by the general formula (I) or salts thereof possess excellent insecticidal effects against various insects at low dosage as compared with conventional pest controllers.
The present inventors have earnestly conducted investigation on the aminoquinazolinone (thione) derivatives for developing a novel pest controller having expanded insceticidal spectrum. Finally, the inventors have found the fact that novel aminoquinazolinone derivatives having bromine atom, iodine atom, perfluoroalkyl group, perfluoroalkoxy group or the like in the quinazoline ring possess quite excellent insecticidal activities as pest controllers.
The present invention relates to substituted aminoquinazolinone (thione) derivatives represented by the general formula (I), or salts thereof: 
[where R is a hydrogen atom; a hydroxyl group; a formyl group; a (C1-12)alkyl group; a halo(C1-6)alkyl group; a hydroxy(C1-6)alkyl group; a (C2-6)alkenyl group; a (C2-6)-alkynyl group; a (C1-6)alkoxy group; a halo(C1-6)alkoxy group; a (C1-6)alkoxy(C1-3)alkyl group; a (C1-6)alkoxy(C1-3)alkoxy(C1-3)alkyl group; a (C1-6)alkylthio group; a halo(C1-6)alkylthio group; a (C1-6)alkylsulfinyl group; a (C1-6)alkylsulfonyl group; a (C1-6)alkylthio(C1-3)alkyl group; a di(C1-6)alkoxy(C1-3)alkyl group in which the (C1-6)alkoxy groups may be the same or different; an unsubstituted amino(C1-6)alkyl group; a substituted amino(C1-6)alkyl group having one or two substituents which may be the same or different and are selected from the group consisting of (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C2-6)alkenyl groups and (C2-6)alkynyl groups; a cyano(C1-6)alkyl group; a (C1-6)alkylcarbonyl group; a (C1-6)alkoxycarbonyl group; a hydroxycarbonyl-(C1-3)alkyl group; a (C1-6)alkoxycarbonyl(C1-3)alkyl group; an unsubstituted aminocarbonyl group; a substituted aminocarbonyl group having one or two substituents which may be the same or different and are selected from the group consisting of (C1-6)alkyl groups, (C2-6)alkenyl groups and (C2-6)alkynyl groups; a (C3-6)-cycloalkyl(C1-3)alkyl group; an unsubstituted phenyl(C1-3)alkyl group; a substituted phenyl(C1-3)alkyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted phenylcarbonyl group; a substituted phenylcarbonyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted phenylthio group; a substituted phenylthio group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted phenyl-sulfonyl group; a substituted phenylsulfonyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted phenyl(C1-6)alkylsulfonyl group; a substituted phenyl(C1-6)alkylsulfonyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted phenyloxycarbonyl group; a substituted phenyloxycarbonyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)-alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)-alkylthio groups; an unsubstituted phenyloxy(C1-3)alkyl group, a substituted phenyloxy(C1-3)alkyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted phenyl(C2-6)-alkenyl group, a substituted phenyl(C2-6)alkenyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups, halo(C1-6)alkylthio groups and (C1-2)alkylenedioxy groups; an unsubstituted phenyl(C2-6)alkynyl group; a substituted phenyl(C2-6)alkynyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups, halo(C1-6)alkylthio groups and (C1-2)alkylenedioxy groups; an unsubstituted phenyl(C2-4)alkynyl(C1-3)alkyl group; a substituted phenyl(C2-4)alkynyl(C1-3)alkyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups, halo(C1-6)alkylthio groups and (C1-2)alkylenedioxy groups; a 1,3-dioxolan-2-yl(C1-3)alkyl group; or a phthalimido(C1-6)alkyl group,
R1 is a 5- or 6-membered heterocyclic ring having 1 to 3 heteroatoms which may be the same or different and are selected from the group consisting of oxygen atom, sulfur atom and nitrogen atom, said heterocyclic ring may have 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups and (C1-6)alkoxy groups, and the nitrogen atom in the heterocyclic ring may form an N-oxide group,
Y is an oxygen atom or a sulfur atom,
Z is
xe2x80x94N=C(R2)xe2x80x94
(wherein R2 is a hydrogen atom, a (C1-6)alkyl group or a halo(C1-6)alkyl group), or
xe2x80x94N(R3)xe2x80x94CH(R2)xe2x80x94
(wherein R2 is as defined above, and R3 is a hydrogen atom, a (C1-6)alkyl group, a formyl group, a (C1-3)-alkylcarbonyl group or a halo(C1-3)alkylcarbonyl group),
X may be the same or different, and is a bromine atom, an iodine atom; a hydroxyl group; a cyano group; a (C1-6)alkyl group; a halo(C1-10)alkyl group; a (C2-6)alkenyl group; a halo(C2-6)alkenyl group; a (C2-6)alkynyl group; a (C1-6)alkoxy group; a halo(C1-6)alkoxy group; a (C1-6)alkylthio group; a halo(C1-6)alkylthio group; a (C1-6)alkylsulfinyl group; a halo(C1-6)alkylsulfinyl group; a (C1-6)alkylsulfonyl group; a halo(C1-6)alkylsulfonyl group; a halo(C1-6)alkoxyhalo(C1-6)alkoxy group; a carboxyl group; a (C1-6)alkoxycarbonyl group; an unsubstituted aminocarbonyl group; a substituted aminocarbonyl group having one or two substituents which may be the same or different and are selected from the group consisting of (C1-6)alkyl groups, (C2-6)alkenyl groups and (C2-6)alkynyl groups; a carboxy(C1-6)alkyl group; a (C1-6)alkoxycarbonyl(C1-3)alkyl group; an unsubstituted aminocarbonyl(C1-3)alkyl group; a substituted aminocarbonyl(C1-3)alkyl group having one or two substituents which may be the same or different and are selected from the group consisting of (C1-6)alkyl groups, (C2-6)alkenyl groups and (C2-6)alkynyl groups; a sulfonic acid group; an unsubstituted aminosulfonyl group; a (C1-6)alkoxysulfonyl group; a substituted aminosulfonyl group having one or two substitutents which may be the same or different and are selected from the group consisting of (C1-6)alkyl groups, (C2-6)alkenyl groups and (C2-6)alkynyl groups; an unsubstituted phenyl group; a substituted phenyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups, halo(C1-6)alkylthio groups, (C1-6)alkoxysulfonyl groups and a substituted aminosulfonyl groups having one or two substituents which may be the same or different and are selected from the group consisting of (C1-6)alkyl groups, (C2-6)alkenyl groups and (C2-6)alkynyl groups; an unsubstituted phenyl(C1-3)alkyl group; a substituted phenyl(C1-3)alkyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted phenyloxy group; a substituted phenyloxy group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted pyridyloxy group; or a substituted pyridyloxy group having one or more substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-C6)alkythio groups and halo(C1-6)alkylthio groups; and n is an integer of 0 to 4], pest controllers containing the substituted amino-quinazolinone (thione) derivative or salts thereof as the active ingredient, and a method for using the pest controllers.
The present invention also relates to intermediate compounds for producing the above-mentioned derivatives, represented by the general formula (II): 
[wherein, X may be the same or different and is a bromine atom, an iodine atom; a hydroxyl group; a cyano group; a (C1-6)alkyl group; a halo(C1-10)alkyl group; a (C2-6)alkenyl group; a halo(C2-6)alkenyl group; a (C2-6)alkynyl group; a (C1-6)alkoxy group; a halo(C1-6)alkoxy group; a (C1-6)alkylthio group; a halo(C1-6)alkylthio group; a (C1-6)alkylsulfinyl group; a halo(C1-6)-alkylsulfinyl group; a (C1-6)alkylsulfonyl group; a halo(C1-6)alkylsulfonyl groups; a halo(C1-6)alkoxyhalo(C1-6)alkoxy group; a carboxyl group; a (C1-6)alkoxycarbonyl group; an unsubstituted aminocarbonyl group; a substituted aminocarbonyl group having one or two substituents which may be the same or different and are selected from the group consisting of (C1-6)alkyl groups, (C2-6)alkenyl groups and (C2-6)alkynyl groups; a carboxy(C1-6)alkyl group; a (C1-6)alkoxycarbonyl(C1-3)alkyl group; an unsubstituted aminocarbonyl(C1-3)alkyl group; a substituted aminocarbonyl(C1-3)alkyl group having one or two substituents which may be the same or different and are selected from the group consisting of (C1-6)alkyl groups, (C2-6)alkenyl groups and (C2-6)alkynyl groups; a sulfonic acid group; a (C1-6)alkoxysulfonyl group; a sulfonamide group having a hydrogen atom, a (C1-6)alkyl group, a (C2-6)alkenyl group or a (C2-6)alkynyl group on the nitrogen atom; an unsubstituted phenyl group; a substituted phenyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted phenyl(C1-3)alkyl group; a substituted phenyl(C1-3)alkyl group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)-alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)-alkylthio groups; an unsubstituted phenyloxy group; a substituted phenyloxy group having on the ring 1 to 5 substituents which may be the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkylthio groups and halo(C1-6)alkylthio groups; an unsubstituted pyridyloxy group; or a substituted pyridyloxy group having one or more substituents which may the same or different and are selected from the group consisting of halogen atoms, nitro groups, cyano groups, (C1-6)alkyl groups, halo(C1-6)alkyl groups, (C1-6)alkoxy groups, halo(C1-6)alkoxy groups, (C1-6)alkythio groups and halo(C1-6)alkylthio groups; n is an integer of 0 to 4; and Y is an oxygen atom or a sulfur atom].
The pest controllers of the present invention containing, as the active ingredient, substituted aminoquinazolinone (thione) derivatives or salts thereof represented by the general formula (I) possess excellent insecticidal effect at low dosage against greenhouse whitefly (Trialeurodes vaporariorum) and the like, which conventional compounds having similar chemical structures do not show insecticidal effects. Thus, the substituted aminoquinazolinone (thione) derivatives of the present invention are excellent pest controllers as compared with conventional ones.
In the definitions of each substituents of the substituted aminoquinazolinone (thione derivatives of the general formula (I) of the present invention, the xe2x80x9chalogen atomxe2x80x9d means a chlorine atom, a bromine atom, an iodine atom or a fluorine atom. The term xe2x80x9c(C1-12)xe2x80x9d means 1 to 12 carbon atoms. The term xe2x80x9c(C1-12)alkyl groupxe2x80x9d means a linear or branched alkyl group of 1 to 12 carbon atoms, for example an alkyl group such as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl and the like. The term xe2x80x9chalo(C1-10)alkyl groupxe2x80x9d means a substituted and linear or branched alkyl group of 1 to 10 carbon atoms having, as the substituent(s), one or more halogen atoms which may be the same or different, for example trifluoromethyl group, pentafluoroethyl group, heptafluoropropyl group and the like. The term xe2x80x9c(C2-6)-alkenyl groupxe2x80x9d means a linear or branched alkenyl group of 2 to 6 carbon atoms having one or more double bonds. The term xe2x80x9chalo(C2-6)alkenyl groupxe2x80x9d means a substituted linear or branched alkenyl group of 2 to 6 carbon atoms having, as the substituent(s), one or more halogen atoms which may be the same or different. The term xe2x80x9c(C2-6)alkynyl groupxe2x80x9d means a linear or branched alkynyl group of 2 to 6 carbon atoms having one or more triple bonds. The term xe2x80x9chalo(C2-6)alkynyl groupxe2x80x9d means a substituted linear or branched alkynyl group of 2 to 6 carbon atoms having, as the substituent(s), one or more halogen atoms which may be the same or different. The term xe2x80x9c5- or 6-membered heterocyclic ring having 1 or more heteroatoms which may be the same or different and are selected from the group consisting of oxygen atom, sulfur atom and nitrogen atomxe2x80x9d means any 5- or 6-membered heterocyclic ring for example, furan, thiophene, pyrrole, oxazole, thiazole, pyrazole, imidazole, 1,2,3-thiadiazole, 1,2,4-thiadiazole, 1,2,5-thiadiazole, 1,3,4-thiadiazole, 1,2,4-triazole, pyridine, pyridazine, pyrimidine, pyrazine, pyrrolidine, piperidine, morpholine, thiomorpholine, dithiolane, dithian, piperazine, dioxolan, imidazolidine, tetrahydrofuran and the like.
The substituents of the substituted amino-quinazolinone (thione) derivatives represented by the general formula (I) are preferably as follows: R is a hydrogen atom, a formyl group, a (C1-6)alkyl group, a (C2-6)alkenyl group, a (C2-6)alkynyl group, a (C1-6)-alkylcarbonyl group, a (C1-6)alkoxycarbonyl group, a (C1-6)alkylthio group, a halo(C1-6)alkylthio group, a phenylcarbonyl group, a substituted phenylcarbonyl group, a substituted phenyl(C1-6)alkyl group, a substituted phenyl(C2-6)alkenyl group or a substituted phenyl(C2-6)alkynyl group; R1 is a pyridyl group, particularly 3-pyridyl group; Y is an oxygen atom or a sulfur atom; Z is a group of the formula,
xe2x80x94N(R3)xe2x80x94CH(R2)xe2x80x94
(wherein R2 and R3 are each a hydrogen atom or a (C1-6)-alkyl group); X is a bromine atom, an iodine atom, a halo(C1-6)alkyl group, a halo(C1-6)alkoxy group, a halo(C1-6)alkylthio group, a halo(C1-6)alkylsulfinyl group, a halo(C1-6)alkylsulfonyl group or a phenyl group); and n may be preferably an integer of 0 to 2.
As the salt of the substituted aminoquinazo-linone (thione) derivative of the formula (I), there can be exemplified salts with mineral acids such as hydrochloric acid, sulfuric acid, nitric acid, etc., and salts with alkali metal atoms such as sodium, potassium, etc.
The compound of the formula (II), an intermediate used for producing the substituted amino-quinazolinone (thione) derivative of the formula (I) can be produced by either of the following processes.
Production Process 1 
wherein X and n are as defined above, R4 is a (C1-6)alkyl group, and Hal is a halogen atom.
A compound of the general formula (II-1) can be produced by reacting a compound of the above general formula (III) with hydrazine hydrate in the presence of an inert solvent.
As the inert solvent usable in this reaction, any inert solvent may be used so long as it does not markedly inhibit the progress of the reaction. There can be exemplified alcohols such as methanol, ethanol, propanol, butanol, etc.; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, etc.; aromatic hydrocarbons such as benzene, toluene, xylene, monochlorobenzene etc.; nitrites such as acetonitrile, benzonitrile, etc.; cellosolves such as methyl cellosolve, etc.; ethers such as diethyl ether, diglyme, dioxane, tetrahydrofuran, etc.; amides such as dimethylformamide, dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, 1-methyl-2-pyrrolidone, etc.; dimethyl sulfoxide; sulfolane; and water. These inert solvents may be used singly or as a mixture thereof.
The reaction temperature may be properly chosen in the range of room temperature to the boiling point of the inert solvent used, and ranges preferably from room temperature to 90xc2x0 C.
Since the reaction is an equimolar reaction, it is sufficient that the compound of the general formula (III) and hydrazine hydrate are used in equimolar amounts, though either of these reactants may be used in excess. It is preferable to use hydrazine hydrate in excess.
Although the reaction time is varied depending on the scale of reaction, the reaction temperature, etc., it ranges from several minutes to 48 hours.
After completion of the reaction, the desired compound is isolated from the reaction mixture containing the desired compound by a conventional method, and if necessary, purified by recrystallization, dry column chromatography, etc., whereby the desired compound can be produced.
The compound of the above general formula (III) can be produced according to Collect. Czech. Chem. Commn. (Vol. 55), 752 (1990).
Production Process 2 
wherein R4, X, Y and n are as defined above.
2-1. General Formula (VIII)xe2x86x92General Formula (VI)
A compound of the general formula (VI) can be produced by reacting a compound of the general formula (VIII) with a compound of the general formula (VII) in the presence of an inert solvent and a catalyst.
As the inert solvent usable in this reaction, there can be used, for example, the inert solvents exemplified in production process 1. These inert solvents may be used singly or as a mixture thereof.
As the catalyst, there can be used inorganic acids (e.g. hydrochloric acid and sulfuric acid), acetic acid, p-toluenesulfonic acid, etc. The amount of the catalyst used may be such that the catalyst is present in the reaction system in an amount of 0.001 wt % to 10 wt % based on the weight of the compound of the general formula (VIII).
Since the reaction is an equimolar reaction, it is sufficient that the compound of the general formula (VIII) and the compound of the general formula (VII) are used in equimolar amounts, though either of these reactants may be used in excess.
The reaction temperature may be properly chosen in the range of room temperature to the boiling point of the inert solvent used, and ranges preferably from room temperature to 90xc2x0 C.
Although the reaction time is varied depending on the scale of reaction, the reaction temperature, etc., it ranges from several minutes to 48 hours.
After completion of the reaction, the reaction mixture containing the desired compound is treated in the same manner as in production process 1, whereby the desired compound can be produced.
The compound of the general formula (VIII) may be a commercially available one or may be produced by nitrating a substituted benzaldehyde. Further, the compound of the formula (VIII) can be produced according to the method described in Journal of Chemical Society, 1927, pp. 2375-2378.
2-2. General Formula (VI)xe2x86x92General Formula (V)
A compound of the general formula (V) can be produced by reducing the compound of the general formula (VI) with a reducing agent or by catalytic reduction in the presence or absence of an inert solvent.
As the reducing agent, there can be used, for example, metal hydrides such as, NaBH3CN, LiBH3CN, etc. and reducing agents such as BH3, etc. The amount of the reducing agent used may be properly chosen in the range of 1 mole to excess moles (in terms of the number of moles of hydride as reducing agent) per mole of the compound of the general formula (VI).
As the inert solvent usable in the reaction, any inert solvent may be used so long as it does not markedly inhibit the progress of the reaction. There can be exemplified alcohols such as methanol, ethanol, propanol, butanol, etc.; cellosolves such as methyl cellosolve, etc.; ethers such as diethyl ether, diglyme, dioxane, tetrahydrofuran, etc.; esters such as ethyl acetate, etc.; amides such as dimethylformamide, dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, 1-methyl-2-pyrrolidone, etc.; dimethyl sulfoxide; sulfolane; and water. These inert solvents may be used singly or as a mixture thereof.
The reaction is carried out under acidic or neutral conditions in the pH range of 1 to 7, preferably 4 to 6. It is sufficient that the pH is adjusted by adding hydrogen chloride, hydrogen bromide or the like to the reaction system.
The reaction temperature is chosen in the range of 0xc2x0 C. to the boiling point of the solvent, and ranges preferably from room temperature to 70xc2x0 C.
Although the reaction time is varied depending on the scale of reaction, the reaction temperature, etc., it ranges from several minutes to 48 hours.
After completion of the reaction, the reaction mixture containing the desired compound is treated in the same manner as in production process 1, whereby the desired compound can be produced.
When catalytic reduction is carried out as the reduction reaction, it is carried out according to, for example, the method described in Shin Jikken Kagaku Koza, Vol. 15-11, Maruzen Co., Ltd. As the inert solvent usable in this case, there can be exemplified alcohols such as methanol, ethanol, propanol, butanol, etc.; cellosolves such as methyl cellosolve, etc.; ethers such as diethyl ether, diglyme, dioxane, tetrahydrofuran, etc.; hydrocarbons such as hexane, cyclohexane, etc.; fatty acids or esters thereof, such as acetic acid, ethyl acetate, etc.; amides such as dimethylformamide, dimethylacetamide, 1,3-dimethyl-2-imidazolidinone, 1-methyl-2-pyrrolidone, etc.; and ureas such as tetramethylurea, etc. These inert solvents may be used singly or as a mixture thereof.
As the catalyst used in the reduction reaction, there can be exemplified typical catalysts for catalytic reduction, such as palladium-carbon, palladium black, platinum dioxide, Raney nickel, etc. The amount of the catalyst used may be properly chosen in the range of 0.1% molar equivalent to 5% molar equivalent, preferably 0.5% molar equivalent to 1% molar equivalent, relative to the compound of the general formula (VI).
The hydrogen pressure in the reaction ranges from atmospheric pressure to 300 atmospheres, preferably from atmospheric pressure to 50 atmospheres.
There action temperature may be properly chosen in the range of room temperature to the boiling point of the inert solvent used, and ranges preferably from room temperature to 70xc2x0 C.
Although the reaction time is varied depending on the scale of reaction, the reaction temperature, etc., it ranges from several minutes to 48 hours.
After completion of the reaction, the reaction mixture containing the desired compound is treated in the same manner as in the case of using the reducing agent, whereby the desired compound can be produced.
2-3. General Formula (V)xe2x86x92General Formula (IV)
A compound of the general formula (IV) can be produced by reacting the compound of the general formula (V) with 1,1xe2x80x2-carbonylbis-1H-imidazole (CDI), an alkoxycarbonyl halide, phosgene or thiophosgen in the presence of an inert solvent and in the presence or absence of a base.
As the inert solvent usable in the reaction, there can be exemplified ethers such as diethyl ether, diglyme, dioxane, tetrahydrofuran, etc., and aromatic hydrocarbons such as benzene, toluene, xylene, etc. These inert solvents may be used singly or as a mixture thereof.
As the base, an inorganic base or an organic base may be used, and there can be exemplified inorganic bases such as hydroxides and carbonates of alkali metals and alkaline earth metals [e.g. sodium hydroxide, potassium hydroxide, magnesium hydroxide, sodium carbonate, sodium hydrogencarbonate and potassium carbonate], and organic bases such as triethylamine and pyridine. When CDI is used as a reactant, the reaction can be carried out without a base.
The amount of the base used is 2 moles or more per mole of the compound of the general formula (V).
The reaction temperature may be properly chosen in the range of room temperature to the boiling point of the inert solvent used, and ranges preferably from room temperature to 100xc2x0 C.
Although the reaction time is varied depending on the scale of reaction, the reaction temperature, etc., it ranges from several minutes to 48 hours.
After completion of the reaction, the reaction mixture containing the desired compound is treated in the same manner as in production process 1, whereby the desired compound can be produced.
2-4. General Formula (IV)xe2x86x92General Formula (II)
A compound of the general formula (II) can be produced by hydrolyzing the compound of the general formula (IV) under basic condition in the presence of an inert solvent.
As the inert solvent usable in this reaction, there can be exemplified alcohols such as methanol, ethanol, propanol, butanol, etc.; aromatic hydrocarbons such as benzene, toluene, xylene, etc.; ethers such as diethyl ether, diglyme, dioxane, tetrahydrofuran, etc.; and water. These inert solvents may be used singly or as a mixture thereof.
As the base, there can be used hydroxides of alkali metals or alkaline earth metals, such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, etc.
Depending on the alkyl group for R4, the reaction can be carried out also under acidic conditions by using an organic or inorganic acid such as trifluoroacetic acid or hydrochloric acid.
The reaction temperature may be properly chosen in the range of 0xc2x0 C. to the boiling point of the inert solvent used.
Although the reaction time is varied depending on the scale of reaction, the reaction temperature, etc., it ranges from several minutes to 48 hours.
After completion of the reaction, the reaction mixture containing the desired compound is treated in the same manner as in production process 1, whereby the desired compound can be produced.
Typical examples of the compounds of the general formula (II) produced by production processes 1 and 2 are given in Table 1 but they are not intended in any way to limit the scope of the present invention. In Tables 1, 3 to 4, xe2x80x9cPhxe2x80x9d means phenyl group and xe2x80x9cPyrxe2x80x9d means pyridyl group.
General Formula (II)
Typical examples of process for producing the aminoquinazolinone (thione) derivative of the general formula (I) or salt thereof of the present invention are schematically shown below.
Production Process 3 
wherein R, R1, R2, R3, X, n, Y and Hal are as defined above except that each of R and R3 is not a hydrogen atom.
3-1. General Formula (II) xe2x86x92General Formula (I-1)
An aminoquinazolinone (thione) derivative of the general formula (I-1) can be produced by reacting a compound of the general formula (II) with a compound of the general formula (X) in the presence of an inert solvent and a catalyst.
In the case of this reaction, the desired compound can be produced in a manner similar to that described in production process 2-1.
3-2. General Formula (I-1)xe2x86x92General Formula (I-3)
An aminoquinazolinone (thione) derivative of the general formula (I-3) can be produced by reacting the aminoquinazolinone (thione) derivative of the general formula (I-1) with a compound of the general formula (IX) in the presence or absence of an inert solvent and a base.
As the inert solvent usable in this reaction, there can be used, for example, the inert solvents exemplified in production process 1.
As the base, an inorganic base or an organic base may be used. In addition to the inorganic or organic bases exemplified in production process 2-3, there can also be used alkoxides such as CH3ONa, C2H5ONa, t-C4H9ONa, CH3OK, C2H5OK, t-C4H9OK, etc., and alkali metal hydrides such as NaH, etc. The amount of the base used may be properly chosen in the range of 1 mole to excess moles per mole of the aminoquinazolinone (thione) derivative of the general formula (I-1).
The reaction temperature may be chosen in the range of 0xc2x0 C. to the boiling point of the inert solvent used, and ranges preferably from room temperature to 70xc2x0 C.
Although the reaction time is varied depending on the scale of reaction, the reaction temperature, etc., it ranges from several minutes to 48 hours.
After completion of the reaction, the reaction mixture containing the desired compound is treated in the same manner as in production process 1, whereby the desired compound can be produced.
3-3. General Formula (I-1)xe2x86x92General Formula (I-2)
In the case of this reaction, the desired compound can be produced in a manner similar to that described in production process 2-2.
3-4. General Formula (I-2)xe2x86x92General Formula (I-4)
An aminoquinazolinone (thione) derivative of the general formula (I-4) can be produced by reacting the aminoquinazolinone (thione) derivative of the general formula (I-2) with the compound of the formula (IX) in the presence or absence of an inert solvent and a base.
In the case of this reaction, the desired compound can be produced in a manner similar to that described in production process 3-2.
3-5. General Formula (I-4)xe2x86x92General Formula (I-5)
An aminoquinazolinone (thione) derivative of the general formula (I-5) can be produced by reacting the aminoquinazolinone (thione) derivative of the general formula (I-4) with a compound of the general formula (XI) in the presence or absence of an inert solvent and a base.
In case of this reaction, the desired compound can be produced in a manner similar to that described in production process 3-2.
3-6. General Formula (I-3)xe2x86x92General Formula (I-5)
In case of this reaction, the desired compound can be produced in a manner similar to that described in production process 2-2.
Typical examples of the aminoquinazolinone (thione) derivative of the formula (I) or salt thereof of the present invention are given in Tables 3 and 4 but they are not intended in any way to limit the scope of the present invention.
The abbreviations in Table 3 and Table 4 stand for the following substituents:
c: alicyclic hydrocarbon group
Ph: phenyl group,
Q1: 2-pyridyl group,
Q2: 3-pyridyl group,
Q3: 4-pyridyl group,
Q4: 2-pyridyl-N-oxide group,
Q5: 3-pyridyl-N-oxide group,
Q6: 4-pyridyl-N-oxide group,
Q7: thiazol-5-yl group,
Q8: furan-2-yl group,
Q9: 1,3-dioxolan-2-yl group,
Q10: phthalimid-1-yl group,
Q11: thiophene-2-yl group,
Q12: 5-chloro-1,3-dimethylpyrazole-4-yl group. 